Identification of CDK2 as a novel target in treatment of prostate cancer

Future Oncol. 2018 Apr;14(8):709-718. doi: 10.2217/fon-2017-0561. Epub 2018 Jan 11.

Abstract

Aim: This study aims the potential gene involved in the metastasis of prostate cancer (Pca).

Methods: PubMed GEO datasets (GSE6605 and GSE6606) were downloaded. We used multiple bioinformatics methods to screen differentially expressed genes in Pca. Gene network was built by STRING and visualized by Cytoscape. All of the hub genes were analyzed by cBioPortal. Inhibition of CDK2 including siRNA, inhibitor and cas9-induced CDK2 knockout was followed by an invasion assay. Downstream genes of CDK2 were analyzed by western blot.

Results: Sequencing data were analyzed to screen the genes with expression alterations. The top genes were validated in our samples. 11 hub genes were screened out. Among these genes, STAT3 and CDK2 were significantly associated with recurrence. Further study suggested that inhibition of CDK2 reduced invasion of Pca cell lines. The invasion ability was rescued after reintroduction of CDK2.

Conclusion: These data indicated that CDK2 was a crucial factor in metastasis of Pca and might be a novel therapy target. [Formula: see text].

Keywords: CDK2; GEO database; PI3K/Akt pathway; cBioPortal; cell cycle; hub genes; metastasis; overall survival; prostate cancer; recurrence.

MeSH terms

  • Cell Line, Tumor
  • Computational Biology
  • Cyclin-Dependent Kinase 2 / genetics*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks / genetics
  • Humans
  • Male
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • STAT3 Transcription Factor / genetics*

Substances

  • STAT3 Transcription Factor
  • STAT3 protein, human
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2